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Ambient Ion Soft Landing Abraham K. Badu-Tawiah, Chunping Wu, and R. Graham Cooks* Chemistry Department, Purdue University, West Lafayette, Indiana 47907, United States
bS Supporting Information ABSTRACT: Ambient ion soft landing, a process in which polyatomic ions are deposited from air onto a surface at a specified location under atmospheric pressure, is described. Ions generated by electrospray ionization are passed pneumatically through a heated metal drying tube, their ion polarity is selected using ion deflectors, and the dry selected ions are soft-landed onto a selected surface. Unlike the corresponding vacuum soft-landing experiment, where ions are mass-selected and softlanded within a mass spectrometer, here the ions to be deposited are selected through the choice of a compound that gives predominantly one ionic species upon ambient ionization; no mass analysis is performed during the soft landing experiment. The desired dry ions, after electrical separation from neutrals and counterions, are deposited on a surface. Characterization of the landed material was achieved by dissolution and analysis using mass spectrometry or spectrofluorimetry. The treated surface was also characterized using fluorescence microscopy, which allowed surfaces patterned with fluorescent compounds to be imaged. The pure dry ions were used as reagents in heterogeneous ion/surface reactions including the reaction of pyrylium cations with D-lysine to form the N-substituted pyridinium cation. The charged microdroplets associated with incompletely dried ions could be selected for soft landing or surface reaction by choice of the temperature of a drying tube inserted between the ion source and the electrical ion deflectors.
on soft landing (SL)1,2 is a process in which collisions of hyperthermal polyatomic ions (kinetic energy e 100 eV) at surfaces under vacuum result in deposition of the intact ions or the corresponding molecules at the surface. It occurs competitively with elastic collisions at the surface leading to reflection, surface-induced dissociation, ion/surface reactions such as charge transfer,2 and chemical sputtering.24 Three distinguishable processes have been identified in SL: in one, the landed ion is trapped in its charged form;5,6 in the second the ionized molecule remains structurally intact but it is neutralized and the trapped product is the corresponding neutral molecule.7,8 In the third case the trapped molecule reacts with other deposited species or with functional groups present on the surface, a process often referred to as reactive landing.8,9 It is known that these processes are highly dependent on the physical and chemical properties of the particular surface employed.10,11 The ability to use a mass spectrometer to select the precursor ion and to control its kinetic energy and charge state makes SL an attractive approach for surface modification. It has been used for a variety of applications including selection of pure compounds from complex mixtures,12,13 deposition of mass-selected cluster ions on substrates,1416 biomolecule immobilization for bioactive metal surfaces,17,18 attempts to prepare novel catalytic materials,19,20 and preparation of protein or peptide arrays.7 In principle, SL should provide good spatial resolution although this has not been
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demonstrated. The most significant disadvantage of the technique is its inefficiency, the low ion currents requiring a significant amount of time to deposit useful amounts of material. The primary goal of the current study is to extend ion soft landing to ambient conditions. In this experiment, ions are generated, filtered from neutrals, and soft-landed onto chosen surfaces at approximately specified locations, all at atmospheric pressure. Ions are generated in the open laboratory environment by electrospray ionization (ESI)21 or electrosonic spray ionization (ESSI)22 and passed pneumatically through a heated metal drying tube. Ion polarity is then selected using deflector electrodes, and the dry (or in some cases as noted almost dry) selected ions are soft-landed onto the surface at a specified location determined by the electrodynamic forces involved. Note that the potentials applied to achieve deflection are large, but ion energies impacting the surface must be low given the small mean free path (65 nm) in ambient air.23 The ambient soft landing experiment differs from the corresponding vacuum SL experiment in that particular care must be taken with the choice of the compound to be ionized and the ionization conditions in order to generate and then deposit predominantly a single ionic species. The mass and Received: November 22, 2010 Accepted: February 25, 2011 Published: March 16, 2011 2648
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Scheme 1. (a) Experimental Apparatus. (b) Dimensionsa
a
Straight drying tube: length 7.5 cm, 0.5 cm i.d., 0.6 cm o.d.; single-coil drying tube: length (without coil) 55.5 cm, (coiled loop diameter is 3 cm); i.d. 0.2 cm, o.d. 0.3 cm.
identity of the ions need to be ascertained in advance of the experiment. An important feature of the experiment is the fact that the apparatus allows ions to be separated from neutrals and ion polarity to be selected by choosing the appropriate electrode polarity. As will be shown, the preliminary results of this experiment show deposition of ions of a particular polarity from simple systems and mixtures. The dry ions rather than wet microdroplets were of primary interest for soft landing and ion/surface reactions.
’ EXPERIMENTAL SECTION The apparatus used for ambient ion soft landing (Scheme 1) consisted of an ion source, a drying tube, and ion deflecting and collecting electrodes. The ionization method used was either electrosonic spray ionization (ESSI) or electrospray ionization (ESI); both generate a continuous beam of ions for the entire time period (e120 min.) of the experiment. The drying tube is a stainless steel tube heated with heating tape to an appropriate temperature which was regulated and monitored via an outside wall thermocouple measurement. Two different drying tubes were used: a straight tube was used to create patterned structures on surfaces and for experiments in which the soft landing of charged microdroplets was used. A coiled tube on the other hand was used to achieve high levels of droplet desolvation and so to aid in soft landing of pure dry ions. The evidence for the complete removal of solvent is discussed later. The distance between the ESI/ESSI ion source silicon capillary tip and the drying tube was kept small, ca. 1 mm, to minimize sample loss due to expansion of the ESI spray plume. The dry ions and neutrals emerging from the heated tube were separated, and ion polarity (positive or negative) was selected using ion deflectors, with an appropriate voltage (e.g., 6 kV for positive ion collection) being supplied to the collector plate. The dry selected ions were soft-landed onto the surface. The collection electrode voltage corresponds to an electric field strength of 600 kV/m over the distance of 1 cm used in a typical experiment. Higher fields could not be used because of the onset of discharges, and lower fields were not effective in deflecting ions, yielding large, poorly focused ion spots. The other two electrodes are grounded, as shown in Scheme 1a. Field penetration through the aperture in the middle electrode draws ions toward this surface. The middle electrode serves two purposes: it blocks stray ions from reaching the collection surface and it allows control of the size and shape of the surface spot. The middle electrode consisted of aluminum metal of different thickness ranging from 1 to 15 mm with a central aperture. The aperture shapes examined included circular
(1 cm in diameter), conical (top vs bottom: 1 vs 0.25 cm), and triangular (1 cm base). Sample solutions were typically 501000 ppm of organic salts having polyatomic counterions, (see Supporting Information for details) dissolved in acetonitrile or methanol. Acridine orange, 9,10-bis(phenyethynyl) anthracene, and sulforhodamine 101 were used in the fluorescence experiments. The sample solutions were electrosprayed using a spray voltage of (7 kV, nebulizer gas (N2) pressure of 80120 psi, and sample injection rate for ESSI of 5 μL/min. After soft landing, the spots on which ions had impinged were washed and characterized using mass spectrometry (Thermo LTQ linear ion trap, Thermo Scientific, San Jose, CA). The spot was usually washed with 1050 μL of methanol/ water (1:1) for mass spectrometry which was performed using a nanoESI source unless otherwise stated. In other experiments, a spectrofluorimeter (Varian Cary Eclipse, Varian, Inc. Walnut Creek, CA, or Hitachi F-2000, Hitachi Ltd., Vista, CA) was used to analyze and characterize the soft-landed material after washing from the surface with methanol. Fluorescence microscopy (Olympus BX-51 fitted with a mercury burner) was also used for direct characterization of the thin film present on the surface. Heating Effects. The electrospray plume containing ions to be soft-landed was dried using a heated, coiled tube (one turn) in order to land dry ions rather than microdroplets. A heated, coiled tube (two turns) has previously been used to dry and then fragment peptide ions emerging from an ESSI ion source at atmospheric pressure.24 Those results indicated that fragment ions exiting the tube can be directly analyzed by mass spectrometry. They also showed that the neutral fragments can be characterized after a gas-phase reionization step. During these earlier experiments, the fragment ions were deflected by the use of an ion switch (two parallel plates biased with positive or negative voltages) and the undeflected neutral species were passed through a corona discharge for (re)ionization. The results showed that dry neutral molecules were involved since their mass spectra complemented those recorded for the fragment ions when no ion switch was used. In the present work, the coiled tube is used only for drying. Evidence for complete drying of the charged microdroplets is seen in the fact that free gas-phase cations or anions are collected at surfaces when generated from organic salts (e.g., 1-hexyl-3-methylimidazolium tetrafluoroborate) and dried by being passed through the single-coiled tube heated to >150 °C. Ion polarities of interest were selected using an appropriate electrode voltage polarity without collection of their counterions (Figure S1, Supporting Information). Cation fragmentation was also observed in this experiment when using a single-coil tube heated to 350 °C (Figure S2, Supporting Information). 2649
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Figure 1. Ambient ion soft landing (15 min) of chemical species in a mixture consisting of 1-hexyl-3-methylimidazolium tetrafluoroborate and sodium tetraphenylborate using different polarities and employing a single-coil drying tube. NanoESI mass spectra of negatively (a and b) and positively (c and d) charged microdroplets collected without heating the coiled drying tube; heating the tube to 150 °C resulted in pure anions (e and f) and pure cations (g and h) reaching the surface when positive and negative voltage polarities, respectively, were applied to the collection electrode. Inserts in Figure 1a,c,g represents MS2 product ion spectra of the soft-landed cation at m/z 167 and those in Figure 1b,d,f all represent MS2 product ion spectra of the softlanded anion at m/z 319. Figure 1e,h inserts are magnified (>10 times) versions of the respective spectra.
’ RESULTS AND DISCUSSION Mass Spectrometric Detection of Products of Ambient Ion Soft Landing. Atmospheric pressure ion soft landing (15 min) of
the anions or cations from a mixture consisting of 1-hexyl-3methylimidazolium tetrafluoroborate and sodium tetraphenylborate was performed using the apparatus shown in Scheme 1a and fitted with a coiled drying tube. Mass spectra were recorded in the positive and negative ion modes for each soft-landed
chemical species (Figure 1). For example, Figure 1e,f shows the mass spectra recorded in each polarity after soft landing tetraphenylborate anions using a positively biased collection electrode while Figure 1g,h shows the mass spectra corresponding to 1-hexyl-3-methylimidazolium cations soft-landed using a negatively biased collection electrode. The ESSI source itself can be operated in either polarity; a positive potential was chosen for positive ions generation and vice versa. When no heat was 2650
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Analytical Chemistry Scheme 2. Collision-Induced Dissociation (CID) of 1-Hexyl-3-methylimidazolium Cations
supplied to the drying tube, charged microdroplets containing cationic and anionic species present in the starting salt mixture (1-hexyl-3-methylimidazolium cation (m/z 167), tetrafluoroborate, (m/z 87), and tetraphenyl boron anions (m/z 319)) were collected at the soft landing position, with the focused ion spot being easily visualized. The spot is on the millimeter scale, but its actual size and shape depend on details of the configuration of the middle electrode, size of the drying tube, and the magnitude of the voltage applied to the collection electrode. The identity of the deposited species was confirmed by dissolution and nanospray MS analysis (Figure 1ad). At a drying tube temperature of 150 °C pure positive or negative ions of interest were soft-landed without detectable amounts of signals due to ions of the opposite polarities (ion spot slightly visible, about 1 mm in diameter). For example, only pure intact tetraphenylborate anions appear to have been soft-landed during a 15 min experiment (Figure 1e,f) without the collection of the counter cations (Na, m/z 23) or 1-hexyl-3-methylimidazolium cations when a positive voltage was applied to the collection electrode and the soft landing experiment itself was performed using negative ion mode ESSI. Likewise, pure 1-hexyl-3-methylimidazolium cations were collected (Figure 1g,h) on a negatively biased collection electrode with no observation of its counteranion (BF4, m/z 87) or anions from tetraphenylborate when a negative voltage was applied to the collection electrode and the positive ion mode ESSI was used. Collection of adequate amounts of smaller inorganic ions (e.g., Naþ and BF4) was found typically to require significant amounts of time so interest was focused on organic ions. The chemical identity of the collected ions was confirmed by tandem MS analysis (inserts in Figure 1ad,f,g). For example, upon CID, the 1-hexyl-3-methylimidazolium cations showed the formation of a signal at m/z 83 arising from the loss of 1-hexene, as illustrated in Scheme 2. MS/MS experiments on BF4, m/z 87, were not successful even during negative droplet collection and even for authentic samples (probably due to the high critical energy of dissociation; the F2BF bond dissociation energy is 7.34 eV25), and so the 10B/11B isotopic ratio was used to confirm the collection of BF4 species (Figure 1b insert). Note also that most background peaks in Figure 1 vary with the condition of the instrument; collection of stable species (e.g., organic ions) for 1 h eliminates almost all background peaks (compare Figure 1c, recorded for 15 min soft landing with Figure S1a, Supporting Information, recorded for 1 h). Spectroscopic Characterization of Products of Ambient Ion Soft Landing. A mixture consisting of two fluorescent compounds (9,10-bis(phenylethynyl)anthracene and sulforhodamine 101) was ionized by electrospray, and the dry ions resulting from passage through the coiled heated (150 °C) drying tube were soft-landed under ambient conditions. As expected, the nonpolar component of the mixture, 9,10-bis(phenylethynyl)anthracene did not contribute to the electrospray ionization mass spectrum, confirming that only ions reach the surface. The ions resulting from sulforhodamine 101 (MW 606) were selectively deflected electrically and soft landed as pure material. In
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separate experiments, the cations (m/z 607) and anions (m/z 605) of sulforhodamine 101 were landed, the surface was washed, and the collected material was analyzed using spectrofluorimetry. After soft landing of cations for 8 h (the long time being used because of the limited number of cations generated by ESSI using a neutral solution of sulforhodamine 101), the treated ion spot was washed with 220 μL of methanol, and the resulting solution was analyzed using the Varian Cary Eclipse spectrofluorimeter. A fluorescence emission spectrum recorded using an excitation wavelength of 550 nm showed the presence of sulforhodamine 101 in the collected sample (Figure 2c). At an excitation wavelength of 390 nm, no fluorescence emission was observed in the soft-landed sample, except for the interfering emission spectrum with a maximum wavelength of 600 nm, arising from sulforhodamine 101 which also absorbs light at 390 nm, Figure 2d. This finding indicates the absence of 9,10-bis(phenylethynyl)anthracene on the collection electrode. Analysis of the authentic mixture confirms this conclusion (Figure 2a,b). Pure negative ions of sulforhodamine 101 were soft-landed for 3 h, using the coiled heating tube, washed with 1 mL methanol, and detected using the Hitachi F-2000 spectrofluorimeter (Figure S3, Supporting Information). Note that soft landing (1 h and then washing the ion spot with 1 mL of methanol) of negatively charged microdroplets (without heating) was shown to result in deposition of both 9,10-bis(phenylethynyl)anthracene and sulforhodamine 101 (Figure S3d,e). This result also confirms the role of heating in allowing pure ions to be landed. The ambient ion soft landing apparatus therefore allows electrospray ionization to be used to produce pure materials from simple mixtures at atmospheric pressure. The efficiency of the process is low. In another experiment, the pure deposited fluorescent material (presumably in a neutralized form) was washed off the surface and analyzed by mass spectrometry (Figures S4 and S5, Supporting Information). With mass spectrometry using nanospray ionization (allowing smaller sample volumes to be used), the soft landing period need not be long for the deposited products to be observed. It is also straightforward to record MS/MS data on selected ions to confirm their identity through formation of characteristic fragments. In the case of sulforhodamine 101, both the protonated (M þ H)þ and deprotonated (M H) ions fragment predominantly through the loss of SO3 neutral species. In addition to spectrofluorimetric and mass spectrometric analysis of the soft-landed ions, the treated ion spots/films present on the surface were also analyzed by fluorescence microscopy which provided a selective means of imaging ions present on the surface after soft landing (Figure S6, Supporting Information) and characterizing the spot size, which was typically 2 mm in diameter. The ion spot also need not be visible for characterization using this technique. Ion/Surface Reactions. As has been shown, charged droplets as well as dry ions (cations and anions) can be deposited at predetermined locations on a surface. The following experiments focus on whether dry ions may be utilized in ion/surface reactions under atmospheric pressure conditions. For this purpose, the conversion of pyrylium ions into pyridinium ions26,27 was examined (Scheme 3a). D-Lysine was deposited onto the collection electrode and the solvent allowed to evaporate after which the pyrylium salt (2,4,6-triphenylpyrylium tetrafluoroborate) was electrosprayed and the dried cations directed onto the surface. Figure 3a shows that the product ion corresponding to the norleucyl-substituted pyridinium ion (m/z 437) was formed when pyrylium cations were allowed to impinge onto dry D-lysine 2651
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Figure 2. Fluorescence emission spectra from a mixture consisting of two fluorescent compounds sulforhodamine 101 and 9,10-bis(phenylethynyl)anthracene: (a and b) authentic mixture containing both compounds; (c and d) mixture after soft landing of cations of sulforhodamine 101 using the ambient soft landing apparatus fitted with the coiled drying tube heated to 150 °C. Different excitation energies were used in the left- and right-hand panels.
Scheme 3. (a) Schematic Representation of Atmospheric Pressure Ion/Surface Reactions between 2,4,6-Triphenylpyrylium Cations Derived from Soft Landing and D-Lysine Already Present on the Surface. (b) Collision-Induced Dissociation Pathways for the m/z 439 Product Ion
already present on the collection electrode. This assignment was confirmed by MS/MS analysis (Figure 3b), which showed the formation of a signal at m/z 308 through the loss of 2-amino-5hexenoic acid. Further studies using a blank surface with no
D-lysine deposited on the collection electrode show that the ion at m/z 349, which is also present in typical experiments (Figure 3a), is related to the parent pyrylium ion (possibly a sodiated form of the ring-opened 1,5-hydroxyketone intermediate) since it yields fragment ions of m/z 309 and 331 upon collision-induced dissociation (CID) (data not shown). No m/z 439 ion was observed in this blank study, suggesting it is indeed a product ion from reaction between D-lysine and 2,4,6-triphenylpyrylium cation. Also, comparison of Figure 3a with the mass spectra recorded for the reaction of D-lysine and 2,4,6-triphenylpyrylium tetrafluoroborate in bulk solution (Figure S7, Supporting Information) show that some, at least, of the product ions (m/z 437 and 439) collected after ambient soft landing were formed on the surface before washing. The second major product, represented by the ion of m/z 439, is believed to have formed from a reaction between ring-opened pyrylium cation and the primary amine of the D-lysine followed by a transmethylation, with a loss of ammonia. In other words, this ion retains the pyrylium oxygen.28 This assignment is supported by the fact that it fragments (Figure 3c) to yield m/z 309, which is characterized in turn by its MS3 fragmentation process (Figure 3d) to give m/z 231 by the loss of benzene. This is a known characteristic27 of the pyrylium ion. The m/z 439 ion is a radical cation, which readily loses a hydrogen radical (H 3 ) upon CID (Figure 3c) to give signal at m/z 438 (Scheme 3b). Spatial Patterning. The ambient soft landing apparatus was used to create arrays of ion spots consisting of different fluorescent compounds (Figures S6 and S9, Supporting Information). It is also straightforward to control the shape and size of these ion spots by simply changing the shape and depth of the aperture
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Figure 3. Reactive landing of cations derived from 2,4,6-triphenylpyrylium tetrafluoroborate with D-lysine present on the collection electrode in a heterogeneous surface reaction: (a) nanoESI-MS of the collected ions. MS/MS of reaction product ion at (b) m/z 437 and (c) m/z 439. (d) MS3 of m/z 439 via m/z 309. Soft landing (1 h) was performed using a one-turned coiled tube heated to 150 °C, flow rate of 5 μL/min, N2 gas pressure of 120 psi. Insert in b is MS3 product ion spectrum of ion at m/z 437 and then at m/z 308.
through which the ion beam passes (Figures S8ac and S9, Supporting Information). Spot size is also affected by the magnitude of the voltage supplied to the collection electrode (Figure S10, Supporting Information). The size of the ion spot, using the straight drying tube and a 5 mm middle electrode is typically 2 mm in diameter (Figure S8e). The spot size was reduced from 2 to 0.5 mm by using a 5 mm middle electrode with a 1 0.25 cm conical hole at its center instead of the typical 1 cm circular hole. Although atmospheric pressure ion focusing has been reported previously,29 it is still not clear if the effect observed here is a focusing or a masking effect. Further data and comments on this effect and of other experimental variables on patterning are given in the Supporting Information. However, a comment can be made on the efficiency of ion (positive or negative) extraction from the moving ESI-derived plume of dried ions: about 0.5 μg of material is typically extracted during a 2 h soft landing with the straight tube heated to 350 °C. This corresponds to about 5% of all the ions exiting the ion source (typical ion current at source was measured as about 0.3 μA).
’ CONCLUSIONS Ion soft landing experiments can be performed under ambient conditions as well as in the traditional vacuum environment. A
continuous ion source is combined with a heated tube and a special ion switch24 to achieve soft landing of dry ions at atmospheric pressure. Organic salts and fluorescent compounds have been used to show that electrospray ionization in conjunction with the ambient ion soft landing apparatus allows deposition of ions of a selected polarity. Ambient ion soft landing also presents a simple means of constructive surface patterning with different chemical species, yielding surfaces with defined chemical structures by directly delivering the pure dry ions onto the surface. The surface-patterning procedure yields relatively low spatial resolution but may have advantages over other modes of patterning in terms of the chemical diversity of the reagent ions, and the ease with which they can be selected and landed. Ambient soft landing also enables ion/surface reactions at the interface to be performed as a means of surface modification. The ability to process free gas-phase ions (i.e., generate, filter, control trajectory, deposit, and/or perform reactions) in the open laboratory environment should open new doors to new chemistry and faster ways of accessing and utilizing the products of organic reactions. The flexibility of the ambient soft landing experiment is increased because the surface is completely accessible during the experiment. The shape, size, and composition of the treated ion spot can be controlled using experimental 2653
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Analytical Chemistry variables. The fact that online mass-selection is not required in the ambient ion soft landing experiment makes it a faster process as well as yield higher ion currents (by 2 orders of magnitude) than conventional soft landing under vacuum.
’ ASSOCIATED CONTENT
bS
Supporting Information. Additional information as noted in the text. This material is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION Corresponding Author
*Phone: (765) 494-5262. Fax: (765) 494-9421. E-mail: cooks@ purdue.edu.
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’ ACKNOWLEDGMENT This work was funded by the National Science Foundation (CHE NSF 0848650). ’ REFERENCES (1) Franchetti, V.; Solka, B. H.; Baitinger, W. E.; Amy, J. W.; Cooks, R. G. Int. J. Mass Spectrom. Ion Phys. 1977, 23 (1), 29–35. (2) Gologan, B.; Green, J. R.; Alvarez, J.; Laskin, J.; Cooks, R. G. Phys. Chem. Chem. Phys. 2005, 7 (7), 1490–1500. (3) Hopf, C.; Jacob, W.; von Keudell, A. J. Appl. Phys. 2005, 97, 094904. (4) Meroueh, S. O.; Wang, Y. F.; Hase, W. L. J. Phys. Chem. A 2002, 106, 9983. (5) Miller, S. A.; Luo, H.; Pachuta, S. J.; Cooks, R. G. Science 1997, 275, 1447–1450. (6) Volny, M.; Elam, W. T.; Ratner, B. D.; Turecek, F. Anal. Chem. 2005, 77, 4846–4853. (7) Ouyang, Z.; Takats, Z.; Blake, T. A.; Gologan, B.; Guymon, A. J.; Wiseman, J. M.; Oliver, J. C.; Davisson, V. J.; Cooks, R. G. Science 2003, 301, 1351–1354. (8) Volny, M.; Elam, W. T.; Branca, A.; Ratner, B. D.; Turecek, F. Anal. Chem. 2005, 77, 4890–4896. (9) Hu, Q.; Wang, P.; Gassman, P. L.; Laskin, J. Anal. Chem. 2009, 81, 7302–7308. (10) Dongre, A. R.; Somogyi, A.; Wysocki, V. H. J. Mass Spectrom. 1996, 31 (4), 339–350. (11) Laskin, J.; Futrell, J. H. J. Chem. Phys. 2003, 119 (6), 3413–3420. (12) Mayer, P. S.; Turecek, F.; Lee, H. N.; Scheidemann, A. A.; lney, T. N.; Schumacher, F.; Strop, P.; Smrcina, M.; Patek, M.; Schirlin, D. Anal. Chem. 2005, 77, 4378. (13) Siuzdak, G.; Hollenbeck, T.; Bothner, B. J. Mass Spectrom. 1999, 34, 1087. (14) Mitsui, M.; Nagaoka, S.; Matsumoto, T.; Nakajima, A. J. Phys. Chem. B 2006, 110, 2968. (15) Palmer, R. E.; Pratontep, S.; Boyen, H. G. Nat. Mater. 2003, 2, 443. (16) Rauschenbach, S.; Stadler, F. L.; Lunedei, E.; Malinowski, N.; Koltsov, S; Costantini, G; Kern, K. Small 2006, 2 (4), 540–547. (17) Volny, M.; Elam, W. T.; Branca, A.; Ratner, B. D.; Tureek, F. Anal. Chem. 2005, 77 (15), 4890–4896. (18) Kitching, K. J.; Lee, H.-N.; Elam, W. T.; Johnston, E. E.; MacGregor, H.; Miller, R. J.; Turecek, F.; Ratner, B. D. Rev. Sci. Instrum. 2003, 74, 4832–4839. (19) Kaden, W. E.; Wu, T.; Kunkel, W A.; Anderson, S. L. Science 2009, 326, 826. (20) Vajda1, S.; Pellin, M. J.; Greeley, J. P.; Marshall, C. L.; Curtiss, L. A.; Ballentine, G. A.; Elam, J. W.; Catillon-Mucherie, S.; Redfern, P. C.; Mehmood, F.; Zapol, P. Nat. Mater. 2009, 8, 213–216. 2654
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